The cutaneous covering contains the skin and its annexes. Human skin is constituted, from the outside inward by three different zones: epidermis, dermis and hypoderma. Among its annexes we can quote the pilo-sebaceous follicle, or pilosebaceous unit, formed by the hair and by the sebaceous gland attached to the canal of the hair.
Hairs include a fixed part or a root, implanted in an invagination of the epidermis, the hair follicle, and a free part or a stalk, more or less tapered in its extremity. The root of the hair adheres to the hair follicle and forms, on its base, a bulb hollowed out in its centre where lodge the dermic papilla rich in capillaries with nutritive function. The hair follicles follow a growth cycle composed of three steps: an anagen phase or a phase of growth, a catagen phase or a phase of regression, then a telogene phase or of rest phase. In a human being, the cycles of each hair are not synchronous.
On the base of each hair is annexed a sebaceous gland. The said sebaceous gland secretes an oily semi liquid substance, the sebum, fat acid mixture, triglycerides, cholesterol, cholesterol derivatives and cellular fragments. Sebum production is related at the sebocyte differentiation stage.
The principal function of the mammal hairs is to provide a protection against external environment. But in the human being, this function has gradually disappeared. Hairiness is no longer fashionable in our modern Western societies. Depilation of the body and face is becoming widespread in younger generations living in sophisticated societies who strive after perfection and performance. Thus, in the new cultural paradigms, body hair is associated with a disturbing ancestral image which also acts as the vehicle for a concept of self-negligence, detracting from self-value and unappealing to others.
As for the sebum, secreted by the sebaceous gland at the level of the hair follicle, it lubricates the surface of the skin, hair and hairs, forming a slightly acid oily film, intended to protect the skin against the outside attacks. Contrary to what we thought some years ago, the acne and the oily skin do not go systematically of pair. Indeed, if the acne presents an important occurrence in the cases of androgenic hyper seborrhoea (typically in the case of teenage acnes), it can develop with individuals whose production of sebum is not particularly high. Conversely, individuals with oily skin do not systematically develop acne lesions. So, even with individuals without acne, when the sebum is secreted in excessive quantity, the skin, the hairs and the hair take a glistening aspect which can reveal itself particularly unaesthetic.
For several years, professionals have been looking for means to reduce the sebaceous secretion and to slow down the hair growth of the face or the body.
Not all the various methods intended to reduce the pilosity address the same targets. On the market of cosmetic products, there are many inhibitors of the growth of hairs. As such, we can quote for example inhibitors of 5-alpha reductase (U.S. Pat. No. 4,885,289), ornithine decarboxylase (U.S. Pat. No. 4,720,489), S-adenosylmethionine decarboxylase (U.S. Pat. No. 5,132,293), gamma-glutamyl transpeptidase (U.S. Pat. No. 5,096,911), and transglutaminase (U.S. Pat. No. 5,143,925), cyclooxygenase, 5-lipoxygenase, L-asparagine synthetase, an inhibitor of the retinoic acid activity, an inhibitor of sulfotransferases, an activator of lipoxygenases. Certain approaches target the visible part of the hair (shaving and chemical dissolution). Other ones address both the visible and invisible parts of the hair (wax depilation). Other approaches target the hair bulb (laser method). Methods only targeting the visible part of the hair are ineffective in the long term. Although there are some differences in the efficiency of these methods in terms of duration of re-growth of hairs, their effects are not permanent, which requires a new treatment to remove hairs after a certain time. Reducing the frequency of such treatment is a recurring demand both for men and women.
Besides there are several cosmetic compositions susceptible to be used in anti oily skin treatments. These compositions notably include, as active agents: powders which allow the absorbtion of sebum and consequently engender a matt complexion skin by a mechanical effect; alpha or beta-hydroxyacides; astringent agents which fight against the dilation of the sebaceous follicles; and agents which act on biochemical mechanisms, notably enzymes involved in the production of sebum. However, the efficiency of these compositions is relative, because most do not limit the sebaceous production but only absorb the sebum.
A certain quantity of substances introduced in cosmetics have been produced but there is still room for progress in order to propose satisfying cosmetics capable of slowing down the growth of hairs on the face or the body, and reducing the sebaceous secretion.
We discovered a new means to reduce the activity of the pilosebaceous unit. Indeed, we discovered the interesting properties of protoberberines on the activities of the pilosebaceous unit and in particular on the activities of the hair follicle and the sebaceous gland.
Protoberberines are present in many plants used in traditional medicine and in dietary complements. For example, Goldenseal (=Hydrastis canadensis) is a plant extract containing protoberberines, which has been used for a very long time in traditional medicine, notably by Native Americans as an antiseptic, diuretic and an anti-cancer; it can also be used as a dietary complement and take part in the composition of mouthwashes. We can also quote the use of some protoberberines in an antibacterian treatment, its use as a fungicidal, an anti-protozoon or an antiviral (such as an anti-malaria treatment, anti-HIV, anti-psoriasis), and in an anti-cancer treatment. For example we can underline the use of the chelidonine as a purgative, an antispasmodic, a choleritic either hypotensor or that of Chelidonium majus for its virtues as an anti inflammatory (U.S. Pat. No. 5,997,876), for its anti-bacterian or anti-viral virtues in anti-psoriasis compositions (U.S. Pat. No. 5,165,932), and in the treatment of parodonthopathy (U.S. Pat. No. 5,043,153).
However, it was never suggested using protoberberines to reduce the activity of the pilosebaceous unit, notably to slow down and/or inhibit the growth of hairs and/or hair of the face and/or the body or to prevent and/or to inhibit the seborrheic activity of the sebaceous glands.
We discovered that berberine engenders a toxic effect on the cells of the skin. Surprisingly, we discovered that protoberberines other than berberine, and in particular palmatine, have not this toxic effect on skin cells (see example D). So one of the major technical problems for the inventors was to find a compound allowing to inhibit the activity of the pilosebaceous unit with respect to the balance of the skin so as to limit the toxic effects on the cells of the skin (keratinocyte, fibroblast).